POS0797 EFFICACY AND SAFETY OF TOFACITINIB VERSUS LEFLUNOMIDE TREATMENT IN TAKAYASU ARTERITIS: A PROSPECTIVE STUDY
Authors: J. Wang, X. Dai, L. MA, S. Wu, X. Jin, Z. Ji, H. Chen, L. MA, Z. Ding, L. Jiang, X. Kong
Journal: Annals of the Rheumatic Diseases (2022)

Background Takayasu arteritis (TAK) is a rare large-vessel vasculitis characterized by vascular granulomatous inflammation. TA is more prevalent in young women aged less than 40 years old. It mainly involves aorta and its major branches. Those involved arteries can progress into stenosis and occlusion, which can lead to further ischaemia of the corresponding tissue and life-threatening events. Thus, effective treatment is in need to improve patients’ prognosis. To date, glucocorticoids (GCs) and immunosuppressants remain as the first-line therapy for TAK patients. According to 2021 American College of Rheumatology/Vasculitis Foundation guideline, GCs and immunosuppressants such as methotrexate and azathioprine were recommended as initial therapy [1]. LEF functions as an inhibitor of pyrimidine synthesis. It has been widely used in a variety of autoimmune disease. In TAK treatment, by comparing LEF with methotrexate or cyclophosphamide, LEF showed its superiorities in remission induction, relapse prevention and good tolerance. Tofacitinib (TOF) is a JAK1/JAK3 signaling pathway inhibitor. In TAK, increasing evidence has suggested that JAK/STAT signaling pathway played an essential role in the pathogenesis of TAK [2]. More importantly, according to our recent study, TOF is superior to MTX for complete remission (CR) induction, relapse prevention and GC tapering. However, its efficacy needs further confirmation. Objectives Thus, this study aimed to compare the effectiveness and safety of TOF with another effective agent, LEF in patients with TAK. Methods A total of 67 active patients with TAK were recruited from an ongoing observational TAK cohort. Thirty-five patients were treated with GCs and LEF, and 32 patients were treated with GCs and TOF. The study period was 12 months. The primary endpoint was effectiveness rate (ER) at 6 months. The other aspects were also evaluated at 6 or 12 months, including remission rate and relapse rate, inflammatory parameters reduction, vascular imaging changes, GCs tapering, and side effects. The treatment effect was also evaluated separately among naive or refractory patients between two groups. Results After 6 months’ treatment, no difference was observed in ER between two groups (LEF group: 31/35 (88.57%) vs. TOF group: 28/32 (87.50%), p=1.00). During 12 months’ treatment, the relapse rate was also comparable between two groups (LEF group: 6 (17.14%) vs. TOF group 7 (21.88%), p=0.76,). ESR and CRP were decreased significantly at 6 (ESR: LEF group: p&lt;0.0001; TOF group: p=0.15; CRP: LEF group: p=0.06; TOF group: p=0.007) and 12 months (ESR: LEF group: p&lt;0.0001; TOF group: p=0.06; CRP: LEF group: p=0.006; TOF group: p=0.14) in both groups compared with their corresponding baseline levels. The proportion of patients with imaging improvement after 12 months’ treatment were low in both groups (LEF group: 1 (2.86%) vs. TOF group: 3 (9.38%) p=0.17). After treatment, the doses of GCs were significantly reduced in both groups from the third month onwards compared with their corresponding baseline dose (p&lt;0.05). Among patients with initial GCs dose ≥ 30mg/day, patients in TOF group gained a much lower daily GCs dose than that of LEF group at 9 months and 12 months (p&lt;0.05). Furthermore, the frequency of side effects was higher in LEF group than that of TOF group (12/35, 34.29%, vs 3/32, 9.38%; p=0.02). Conclusion LEF and TOF have comparable treatment effects for patients with TAK. However, TOF is superior to LEF in GCs tapering and safety profile. References [1]Maz M, Chung SA, Abril A, Langford CA, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC et al: 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis. Arthritis Care Res (Hoboken) 2021, 73(8):1071-1087. [2]Zhang H, Watanabe R, Berry GJ, Tian L, Goronzy JJ, Weyand CM: Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis. Circulation 2018, 137(18):1934-1948. Disclosure of Interests None declared